Lysosomes

Question 1

In what cells are lysosomes found?

Answer 1

Most except RBCs

Question 2

How are macromolecules delivered to lysosomes?

Answer 2

By endocytosis and autophagy

Question 3

What enzyme do lysosomes contain?

Answer 3

Hydrolases

Question 4

How is lysosomal pH maintained?

Answer 4

Vacuolar proton pump, to keep acidic pH optima

Question 5

Where do lysosomes transport the products of degradation to?

Answer 5

Cytosol

Question 6

Material destined for degradation is delivered by what 3 pathways

Answer 6

Phagocytosis, autophagy and endocytosis

Question 7

What is endocytosis materia

Answer 7

Extracellular material and plasma membrane proteins

Question 8

What is autophagy material

Answer 8

Material from cytosol and whole cytoplasmic organelles

Question 9

What are phagocytosis material

Answer 9

Large extracellular particulate species like microbes

Question 10

What is autophagy as a process?

Answer 10

Constitutive process removing cytoplasmic components, enchances by cell starvation

Question 11

What is macroautophagy

Answer 11

A type of autophagy, removes old organelles, aggregates of proteins and long-lived proteins by autophagasome. It fuses with lysosome

Question 12

Lysosome involvement in apoptosis

Answer 12

Increased permeability of lysosomal membrane, release of lysosomal proteases called cathepsins into cytosol

Question 13

Lysosomes in plasma membrane repair

Answer 13

Lysosomes act as a reserve membrane to repair holes, triggered by influx of Ca2+ into cell detected by lysosomal membrane protein synaptotagmin 7

Question 14

What is I-cell disease?

Answer 14

Autosomal recessive disorder which causes fromation of intracellular inclusions

Question 15

What mutation is I-cell disease from?

Answer 15

GNPTA which encodes enzyme N-acetylglucosimine-1-phosphotransferase

Question 16

What is mucolipidosis type II otherwise called

Answer 16

I-cell disease

Question 17

I-cell disease features

Answer 17

Facial and skeletal abnormalities
Severe impairment of mental abilities and movement
Heart failure in first ten years

Question 18

Is there a cure for I-cell disease

Answer 18

No

Question 19

Molecular basis for I-cell disease

Answer 19

Reduced intracellular levels of lysosomal hydrolases. No modified by N-acetylglucosamine-1-phosphotransferases hydrolases, so aren’t recognised by M6P receptors and are secreted

Question 20

What is N-acetylglucosamine-1-phosphotransferase is involved in?

Answer 20

Modification of mannosylated glucans attatched to newly synthesised lysosomal hydrolases to produce M6P tag

Question 21

What is Pompe disease caused by?

Answer 21

Autosomal recessive mutations in gene that encodes the lysosmal hydrolase lysosomal acid alpha-D-glucosidase

Question 22

Clinical symptoms of Pompe disease

Answer 22

Progressive cardiac and skeletal myopathy
Infantile- disease occurs in first year

Question 23

What does alpha-D-glucosidase do?

Answer 23

Lysosomal alpha-D-glucosidase cleaves glycogen into glucose that can be transported into the cytosol

Question 24

Molecular basis of pompe disease

Answer 24

Deficiency in lysosomal ⍺-D-glucosidase
causes the abnormal accumulation of glycogen in cells and
the resultant symptoms of the disease

Question 25

How is Pompe disease treated?

Answer 25

Enzyme replacement therapy, by IV infusions of M6P modified alpha-D-glucosidase.

Question 26

What muscle is ERT most effective in (pompe)

Answer 26

Cardiac

Question 27

What is Fabry disease?

Answer 27

X-linked disorder that results from mutations in alpha-galactosidase

Question 28

What are the symptoms of Fabry disease?

Answer 28

Facial abnormalities, renal and cardiac problems

Question 29

What are the symptoms of Fabry disease from?

Answer 29

Deposition of glycolipid Gb3 in walls of many vessels

Question 30

What is the function of alpha-galactosidase

Answer 30

Removes terminal galactose from glycolipid globotriaosylceramide (gb3)

Question 31

Molecular mechanism of Fabry disease

Answer 31

Lack of ⍺-galactosidase activity results in accumulationof Gb3 and in lysosomes and lipid droplets in many celltypes

Question 32

Fabry disease treatments

Answer 32

ERT and Migalastat

Question 33

How does ERT treat Fabry disease?

Answer 33

Administrating M6P modified form of enzyme

Question 34

How does Migalastat treat Fabry’s disease?

Answer 34

Binds to alpha-D-glucosidase mutants in ER and stabilises them to be trafficed to lysosomes where the low pH allows drug to dissociate and enzyme to function

Question 35

Infantile sialic acid storage disease is caused by… (ISASD)

Answer 35

Autosomal recessive mutations in sialin gene

Question 36

ISASD symptoms?

Answer 36

facial abnormalities, intellectual disability and enlarged heart, liver and spleen. Death within 2 years

Question 37

What is Salla disease caused by?

Answer 37

Mutations in sialin gene

Question 38

In what population is Salla disease?

Answer 38

Finnish

Question 39

Which is more severe Salla or ISASD?

Answer 39

ISASD

Question 40

What is sialin

Answer 40

Lysosomal membrane transporter that transports sialic acids from lysosome to cytosol

Question 41

Molecular basis of infantile sialic storage disease and Salla disease

Answer 41

Loss of sialin transport activity results in accumulation of sialic acids in lysosomes